Published online April 14, 2008
doi:10.1084/jem.20071978
The Journal of Experimental Medicine, Vol. 205, No. 5, 1063-1075
The Rockefeller University Press, 0022-1007 $30.00
© 2008 Yang et al.
Regulation of inflammatory responses by IL-17F
Xuexian O. Yang1,
Seon Hee Chang1,
Heon Park3,
Roza Nurieva1,
Bhavin Shah1,
Luis Acero1,
Yi-Hong Wang1,
Kimberly S. Schluns1,
Russell R. Broaddus2,
Zhou Zhu4, and
Chen Dong1
1 Department of Immunology and 2 Department of Pathology, M.D. Anderson Cancer Center, Houston, TX 77030
3 Department of Immunology, University of Washington, Seattle, WA 98195
4 Johns Hopkins University, Baltimore, MD 21224
CORRESPONDENCE Chen Dong: cdong{at}mdanderson.org
Although interleukin (IL) 17 has been extensively characterized, the function of IL-17F, which has an expression pattern regulated similarly to IL-17, is poorly understood. We show that like IL-17, IL-17F regulates proinflammatory gene expression in vitro, and this requires IL-17 receptor A, tumor necrosis factor receptor–associated factor 6, and Act1. In vivo, overexpression of IL-17F in lung epithelium led to infiltration of lymphocytes and macrophages and mucus hyperplasia, similar to observations made in IL-17 transgenic mice. To further understand the function of IL-17F, we generated and analyzed mice deficient in IL-17F or IL-17. IL-17, but not IL-17F, was required for the initiation of experimental autoimmune encephalomyelitis. Mice deficient in IL-17F, but not IL-17, had defective airway neutrophilia in response to allergen challenge. Moreover, in an asthma model, although IL-17 deficiency reduced T helper type 2 responses, IL-17F–deficient mice displayed enhanced type 2 cytokine production and eosinophil function. In addition, IL-17F deficiency resulted in reduced colitis caused by dextran sulfate sodium, whereas IL-17 knockout mice developed more severe disease. Our results thus demonstrate that IL-17F is an important regulator of inflammatory responses that seems to function differently than IL-17 in immune responses and diseases.
Abbreviations used: BALF, bronchoalveolar lavage fluid; CC10, Clara cell 10; CNS, central nervous system; DSS, dextran sulfate sodium; EAE, experimental autoimmune encephalomyelitis; FAP, allergenic fungal proteinase; H&E, hematoxylin and eosin; MEF, mouse embryonic fibroblast; MMP, matrix metalloproteinase; MOG, myelin oligodendrocyte glycoprotein; PAS, periodic acid Schiff; TRAF6, TNFR-associated factor 6.
X.O. Yang and S.H. Chang contributed equally to this study.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
